Spore forming pathogens, such as C. difficile, are important infectious agents. C. difficile is the leading cause of nosocomial diarrhoea in the UK and has been responsible for a significant number of deaths in UK hospitals. Recent figures show a decline in the number of cases in C. difficile infection. However, despite this decrease there are still nearly 10 times as many cases of C. difficile compared to MRSA. PCR ribotype 027 is now the most common ribotype isolated from C. difficile patients, followed by ribotype 106 and 001.
Infected patients excrete large numbers of C. difficile spores and cells into the environment which acts as a reservoir of infection. Patients therefore generally acquire the organism by ingestion of its spores from the contaminated environment. Once ingested the spores are able to survive the acidic environment of the stomach and pass into the GI tract where they germinate into vegetative cells to produce toxins A and B, which may cause disease in susceptible patients.
Spore germination is an irreversible process in which a highly resistant, dormant spore is transformed into a metabolically active cell. Germination occurs in several stages; the first being activated by the binding of germinant receptor on the plasma membrane. This is then followed by the loss of heat resistance and various cations including potassium, hydrogen and sodium and the complex of calcium and dipicolinic acid (DPA). This results in the partial re-hydration of the core, however the organism does not become fully hydrated until the cortex is degraded. As the cortex hydrolyses, the small acid soluble proteins are degraded and the metabolic activity of cell is resumed.
It is known in the art that C. difficile may be simulated to sporulate by exposure to germination solutions comprising a combination of glycine and taurocholate. The transition from the spore state causes the pathogens to be susceptible to attack from antibacterial agents, such chlorhexidine. The aim of the prior art has been to design germinate/exterminate protocols which take advantage of the susceptibility of the pathogen following germination. Such a protocol is shown in FIG. 1. Specifically, attempts have been made in the prior art to design antibacterial solutions which stimulate germination and which have an antibacterial agent to attack the germinated pathogens. However, the antibacterial agents used in such approaches have an inhibitory effect on the germinating solution such that germinate/exterminate approach has had limited success in the clinical setting.
The aim of the present invention is there to provide an alternative antimicrobial composition which overcomes these problems and which is effective against clinically important pathogens.